Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection

J Hepatol. 2017 Feb;66(2):355-362. doi: 10.1016/j.jhep.2016.09.013. Epub 2016 Sep 28.


Background & aims: Cirrhosis related to chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC). The extent to which HCC occurs in U.S. in the absence of cirrhosis in CHB remains unclear.

Methods: We identified CHB patients who were diagnosed with HCC in the national Veterans Administration (VA) between 2001 and 2013. We defined presence and absence of cirrhosis at the time of HCC diagnosis using explicit histological, radiological, endoscopic, and laboratory criteria. We used multivariable regression analysis to identify demographic and clinical characteristics associated with CHB-related HCC in the absence of cirrhosis. We also examined liver transplant-free survival in CHB-HCC patients with and without cirrhosis.

Results: Among 8539 CHB patients, 317 developed HCC of whom 30 (9.5%) did not have any evidence of cirrhosis at the time of HCC diagnosis. Compared to HCC patients with cirrhosis, HCC patients without cirrhosis were more likely to be non-white (African American, OR=6.78; 95% CI 2.05-22.4; Asian, OR 11.6, 95% CI 2.63-50.8), have a family history of HCC (OR 32.9, 95% CI 3.76-288), and hypertension (OR 3.15, 95% CI 1.02-9.75). There was no significant difference in the transplant-free survival between CHB-HCC patients with and without cirrhosis (hazard ratio 0.68, 95% CI 0.43-1.09).

Conclusions: Fewer than 10% of U.S. based CHB-related HCC patients did not have cirrhosis. Race and family history of HCC were the main risk factors for HCC in the absence of cirrhosis in CHB. These factors may help guide the decision to initiate HCC surveillance in CHB patients without cirrhosis.

Lay summary: Patients with chronic hepatitis B who are African American, or Asian, older than 40years of age with family members with liver cancer or high blood pressure are at a higher risk of developing liver cancer in the absence of cirrhosis. These patients should be included in the screening program for liver cancer.

Keywords: Chronic hepatitis B; Cirrhosis; Epidemiology; Hepatocellular carcinoma; Liver cirrhosis; Liver transplantation; Risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Demography
  • Female
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / diagnosis
  • Hepatitis B, Chronic* / epidemiology
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / etiology
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Medical History Taking / statistics & numerical data
  • Middle Aged
  • Risk Factors
  • Socioeconomic Factors
  • Survival Analysis
  • United States
  • United States Department of Veterans Affairs / statistics & numerical data